dbSNP rs3756505: CSNK1A1:c.857+67A>G (chr5-149506960-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001892.6(CSNK1A1):c.857+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,177,532 control chromosomes in the GnomAD database, including 8,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1659 hom., cov: 32)

Exomes 𝑓: 0.11 ( 6417 hom. )

Consequence

CSNK1A1
NM_001892.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

5 publications found

Variant links:

Genes affected

CSNK1A1 (HGNC:2451): (casein kinase 1 alpha 1) Enables protein serine/threonine kinase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; peptidyl-serine phosphorylation; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in centrosome; cytosol; and nuclear speck. Part of beta-catenin destruction complex. Colocalizes with keratin filament and mRNA cleavage and polyadenylation specificity factor complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Apr 2022]

CSNK1A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CSNK1A1	NM_001892.6 link	c.857+67A>G	intron_variant	Intron 8 of 9	ENST00000377843.8	NP_001883.4	P48729-1
CSNK1A1	NM_001025105.3 link	c.941+67A>G	intron_variant	Intron 9 of 10		NP_001020276.1	P48729-2Q6PJ06
CSNK1A1	NM_001271741.2 link	c.857+67A>G	intron_variant	Intron 8 of 9		NP_001258670.1	P48729-3
CSNK1A1	NM_001271742.2 link	c.674+67A>G	intron_variant	Intron 8 of 9		NP_001258671.1	P48729B4DER9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1A1	ENST00000377843.8 link	c.857+67A>G		intron_variant	Intron 8 of 9	1	NM_001892.6	ENSP00000367074.2		P48729-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20878

AN:

152114

Hom.:

1661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.0696

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.106

AC:

109141

AN:

1025300

Hom.:

6417

AF XY:

0.105

AC XY:

54167

AN XY:

517866

show subpopulations

African (AFR)

AF:

0.207

AC:

4953

AN:

23944

American (AMR)

AF:

0.122

AC:

3767

AN:

30806

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

3941

AN:

21516

East Asian (EAS)

AF:

0.183

AC:

6466

AN:

35430

South Asian (SAS)

AF:

0.0606

AC:

4148

AN:

68402

European-Finnish (FIN)

AF:

0.110

AC:

5487

AN:

50046

Middle Eastern (MID)

AF:

0.143

AC:

632

AN:

4428

European-Non Finnish (NFE)

AF:

0.0995

AC:

74155

AN:

745518

Other (OTH)

AF:

0.124

AC:

5592

AN:

45210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4613

9226

13839

18452

23065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.137

AC:

20916

AN:

152232

Hom.:

1659

Cov.:

AF XY:

0.136

AC XY:

10095

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.208

AC:

8638

AN:

41514

American (AMR)

AF:

0.129

AC:

1969

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3472

East Asian (EAS)

AF:

0.179

AC:

925

AN:

5182

South Asian (SAS)

AF:

0.0705

AC:

340

AN:

4826

European-Finnish (FIN)

AF:

0.0931

AC:

988

AN:

10608

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.102

AC:

6961

AN:

68014

Other (OTH)

AF:

0.137

AC:

290

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

906

1812

2718

3624

4530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.117

Hom.:

1260

Bravo

AF:

0.146

Asia WGS

AF:

0.153

AC:

533

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.8

(source)

DANN

Benign

0.89

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3756505

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over